Sodium Azide → N-(5-(6-(1-(cyclopropylmethyl)-1H-1,2,3-triazol-4-yl)-3H-imidazo[4,5-b]-pyridin-3-yl)-2',4'-difluoro-[1,1'-biphenyl]-3-yl)acetamide

HRID 64157Notes

Reaction equation

HRID 64157 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[N:11]=[CH:10][N:9]([C:12]3[CH:13]=[C:14]([NH:26][C:27](=[O:29])[CH3:28])[CH:15]=[C:16]([C:18]4[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=4[F:25])[CH:17]=3)[C:6]2=[N:7][CH:8]=1)#[CH:2].[N-:30]=[N+:31]=[N-:32].[Na+].Br[CH2:35][CH:36]1[CH2:38][CH2:37]1>CN(C=O)C.[Cu](I)I>[CH:36]1([CH2:35][N:30]2[CH:2]=[C:1]([C:3]3[CH:4]=[C:5]4[N:11]=[CH:10][N:9]([C:12]5[CH:13]=[C:14]([NH:26][C:27](=[O:29])[CH3:28])[CH:15]=[C:16]([C:18]6[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=6[F:25])[CH:17]=5)[C:6]4=[N:7][CH:8]=3)[N:32]=[N:31]2)[CH2:38][CH2:37]1

Participants

6

Reactant 3

HCID 33557Sodium AzideHCID 81503BromomethylcyclopropaneHCID 89500199HCID 89500199, compound

Product 1

HCID 89501238N-(5-(6-(1-(cyclopropylmethyl)-1H-1,2,3-triazol-4-yl)-3H-imidazo[4,5-b]-pyridin-3-yl)-2',4'-difluoro-[1,1'-biphenyl]-3-yl)acetamideYield 82.6%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture N-(5-(6-ethynyl-3H-imidazo[4,5-b]pyridin-3-yl)-2′,4′-difluoro-[1,1′-biphenyl]-3-yl)acetamide (300 mg, 0.77 mmol), sodium azide (76 mg, 1.15 mmol, 1.5 eq.), (bromomethyl)cyclopropane (125 mg, 0.92 mmol, 1.2 eq.), copper iodide (14 mg, 0.07 mmol, 0.1 eq.) in DMF was stirred for 16 h at RT. The mixture was quenched with water and the precipitate formed was filtered and dried to give the crude product which was purified by preparative HPLC to give the product in 82.6% yield (310 mg). 1H NMR (300 MHz, DMSO): δ 10.4 (s, 1H) 8.99 (d, 2H), 8.80 (s, 1H), 8.63 (d, 1H), 8.30 (s, 1H), 7.91 (d, 1H), 7.76-7.68 (m, 2H), 7.49-7.41 (m, 1H), 7.30-7.25 (m, 1H), 4.21 (m, 2H), 2.12 (s, 3H), 1.23 (m, 1H), 0.63-0.60 (2H, d) 0.50-0.48 (2H, d); LC-MS (ESI): Calculated mass: 485.4; Observed mass: 486.1 [M+H]+ (rt: 1.52 min).

Workup

  1. customThe mixture was quenched with water
  2. customthe precipitate formed
  3. filtrationwas filtered
  4. customdried

Sources & evidence

ORD record
ord-a4cb815b11ce4ebdbb7a2d0de89e11c6
Source dataset
uspto-grants-2016_09
Patent number
US09447091B2

Reaction notes

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